Aims/hypothesis We designed a chemically modified, enzyme-resistant peptide with triple-acting properties based on human glucagon with amino acid substitutions aligned to strategic positions in the sequence of glucose-dependent insulinotropic polypeptide (GIP). Methods Y 1 -dA 2 -I 12 -N 17 -V 18 -I 27 -G 28,29 -glucagon (termed YAG-glucagon) was incubated with dipeptidylpeptidase IV (DPP-IV) to assess stability, BRIN-BD11 cells to evaluate insulin secretion, and receptor-transfected cells to examine cAMP production. Acute glucose-lowering and insulinotropic properties of YAG-glucagon were assessed in National Institutes of Health (NIH) Swiss mice, while longer-term actions on glucose homeostasis, insulin secretion, food intake and body weight were examined in high-fat-fed mice. Results YAG-glucagon was resistant to DPP-IV, increased in vitro insulin secretion (1.5-3-fold; p<0.001) and stimulated cAMP production in GIP receptor-, glucagon-like peptide-1 (GLP-1) receptor-and glucagon receptortransfected cells. Plasma glucose levels were significantly reduced (by 51%; p<0.01) and insulin concentrations increased (1.2-fold; p<0.01) after acute injection of YAGglucagon in NIH Swiss mice. Acute actions were countered by established GIP, GLP-1 and glucagon antagonists. In high-fat-fed mice, twice-daily administration of YAGglucagon for 14 days reduced plasma glucose (40% reduction; p<0.01) and increased plasma insulin concentrations (1.8-fold; p<0.05). Glycaemic responses were markedly improved (19-48% reduction; p<0.05) and insulin secretion enhanced (1.5-fold; p<0.05) after a glucose load, which were independent of changes in insulin sensitivity, food intake and body weight.
2. Managing emotions: Having appropriate emotional reactions is a capacity that builds Most peop1.e with a hlgh I Q failin life while people on self-awareness. The ability to modulate with average I Q are successful. The dfference negative affects such as anxiety, anger, and often may be attributable to emotional inteulgence depression is a crucial emotional skill. or E.Q. This study aims at studying the E Q of indviduals using an Indian version of the E Q scale. The results are m t too appealing. Reliability of two dfferent scales are dscussed.
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